The dominant W(42) spotting phenotype results from a missense mutation in the c-kit receptor kinase Journal Article
| Authors: | Tan, J. C.; Nocka, K.; Ray, P.; Traktman, P.; Besmer, P. |
| Article Title: | The dominant W(42) spotting phenotype results from a missense mutation in the c-kit receptor kinase |
| Abstract: | The murine white spotting locus (W) is allelic with the proto-oncogene c-kit, which encodes a transmembrane tyrosine protein kinase receptor for an unknown ligand. Mutations at the W locus affect various aspects of hematopoiesis and the proliferation and migration of primordial germ cells and melanoblasts during development to varying degrees of severity. The W42 mutation has a particularly severe effect in both the homozygous and the heterozygous states. The molecular basis of the W42 mutation was determined. The c-kit protein products in homozygous mutant mast cells were expressed normally but displayed a defective tyrosine kinase activity in vitro. Nucleotide sequence analysis of mutant complementary DNAs revealed a missense mutation that replaces aspartic acid with asparagine at position 790 in the c-kit protein product. Aspartic acid-790 is a conserved residue in all protein kinases. These results provide an explanation for the dominant nature of the W42 mutation and provide insight into the mechanism of c-kit-mediated signal transduction. |
| Keywords: | signal transduction; oncoprotein; genetics; mutation; proto-oncogene proteins; nonhuman; molecular genetics; polymerase chain reaction; mouse; phenotype; animal; cytology; metabolism; mice; cells, cultured; stem cell factor receptor; heredity; gene expression; embryology; protein tyrosine kinase; rna; oncogene; liver; dna; amino acid sequence; molecular sequence data; cell culture; nucleotide sequence; homozygote; murinae; base sequence; protein kinase; cell surface receptor; receptors, cell surface; mast cell; mast cells; receptor protein; protein-tyrosine kinase; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; proto-oncogene protein c-kit; proto oncogene protein c kit; proto oncogene proteins |
| Journal Title: | Science |
| Volume: | 247 |
| Issue: | 4939 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 1990-01-12 |
| Start Page: | 209 |
| End Page: | 212 |
| Language: | English |
| DOI: | 10.1126/science.1688471 |
| PUBMED: | 1688471 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 27 January 2020 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work